Vilazodone hydrochloride, IUPAC name 5-(4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl)benzofuran-2-carboxamide hydrochloride, physiologically acceptable salts thereof and their use in treating certain medical disorders are known from U.S. Pat. No. 5,532,241 and WO 00/72832. Polymorphic forms of Vilazodone hydrochloride are disclosed in WO 02/102794.
Vilazodone was approved by the FDA for the treatment of major depressive disorders on Jan. 21, 2011. It is being marketed under the trade name Viibryd.
WO 02/102794 describes that form III of Vilazodone hydrochloride is the most thermodynamically stable polymorph of Vilazodone hydrochloride at room temperature (see WO 02/102794 page 20, lines 23-26 and FIG. 27). In addition WO 02/10274 describes that form III of Vilazodone hydrochloride is non-hygroscopic, e.g. it takes up water only in minimal amounts when exposed to a humidity of about 90% as shown by DVS (dynamic vapor sorption).
However, the process for the preparation of form III disclosed in WO 02/102794 has serious drawbacks. It comprises dispersing Vilazodone free base in tetrahydrofuran, converting the free base to the hydrochloride by the addition of hydrochloric acid, precipitation of form II (a solvate with tetrahydrofuran) and drying of the obtained tetrahydrofuran solvate at a temperature of at least 100° C. to yield form III.
Tetrahydrofuran is a class 2 solvent with a PDE of 7.2 mg/day and a limit of 720 ppm (see ICH Toxic Q3C (M) Maintenance of Note for Guidance on Impurities: Residual solvents (CPMP/ICH/283/95)). 720 ppm is a limit very difficult to achieve by drying Vilazodone hydrochloride tetrahydrofuran solvate, which releases tetrahydrofuran only under quite harsh conditions.
Thus the disadvantages of the described processes for the preparation of form III of Vilazodone hydrochloride are in contrast with the on the other hand described favorable properties of form III.